Genetic Variant NM_033131.4:c.*185T>C (chr1-228059650-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033131.4(WNT3A):c.*185T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,366,316 control chromosomes in the GnomAD database, including 315,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39765 hom., cov: 33)

Exomes 𝑓: 0.67 ( 275907 hom. )

Consequence

WNT3A
NM_033131.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

31 publications found

Variant links:

Genes affected

WNT3A (HGNC:15983): (Wnt family member 3A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 96% amino acid identity to mouse Wnt3A protein, and 84% to human WNT3 protein, another WNT gene product. This gene is clustered with WNT14 gene, another family member, in chromosome 1q42 region. [provided by RefSeq, Jul 2008]

WNT3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3A	NM_033131.4 link	c.*185T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000284523.2	NP_149122.1	P56704-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT3A	ENST00000284523.2 link	c.*185T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_033131.4	ENSP00000284523.1		P56704-1

Frequencies

GnomAD3 genomes

AF:

0.722

AC:

109620

AN:

151912

Hom.:

39735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.793

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.708

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.712

GnomAD4 exome

AF:

0.673

AC:

817005

AN:

1214286

Hom.:

275907

Cov.:

AF XY:

0.675

AC XY:

393672

AN XY:

583534

show subpopulations

African (AFR)

AF:

0.804

AC:

19177

AN:

23838

American (AMR)

AF:

0.709

AC:

8640

AN:

12178

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

11332

AN:

17306

East Asian (EAS)

AF:

0.776

AC:

22577

AN:

29090

South Asian (SAS)

AF:

0.768

AC:

37852

AN:

49256

European-Finnish (FIN)

AF:

0.738

AC:

21389

AN:

28968

Middle Eastern (MID)

AF:

0.715

AC:

2439

AN:

3410

European-Non Finnish (NFE)

AF:

0.659

AC:

658679

AN:

999888

Other (OTH)

AF:

0.694

AC:

34920

AN:

50352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

15538

31077

46615

62154

77692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18468

36936

55404

73872

92340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.722

AC:

109704

AN:

152030

Hom.:

39765

Cov.:

AF XY:

0.727

AC XY:

54049

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.793

AC:

32906

AN:

41494

American (AMR)

AF:

0.707

AC:

10811

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.655

AC:

2272

AN:

3468

East Asian (EAS)

AF:

0.786

AC:

4031

AN:

5126

South Asian (SAS)

AF:

0.781

AC:

3764

AN:

4820

European-Finnish (FIN)

AF:

0.752

AC:

7977

AN:

10606

Middle Eastern (MID)

AF:

0.750

AC:

219

AN:

292

European-Non Finnish (NFE)

AF:

0.671

AC:

45578

AN:

67924

Other (OTH)

AF:

0.713

AC:

1498

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1614

3228

4843

6457

8071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.687

Hom.:

32089

Bravo

AF:

0.721

Asia WGS

AF:

0.804

AC:

2797

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.42

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over